This work is aimed at developing an understanding of enzyme mechanisms in relation to the practical design of potent antimetabolites, termed "transition state analogs", which resemble intermediates in the enzyme catalyzed transformation of substrates. Groups of enzymes studied include carbohydrate isomerases, hydrolytic enzymes for carbohydrates, peptides and nucleic acid derivatives, and choline acetylase. Transition state analogs are bound by these enzymes very much more tightly than substrates, and may thus be useful in controlling metabolic processes connected with microbial diseases and neoplastic transformation. BIBLIOGRAPHIC REFERENCES: Free Energies of Hydration and Hydrolysis of Gaseous Acetamide, J. Am. Chem. Soc. 98, 1987 (1976). A Vapor Phase Analysis of the Hydrophobic Effect, J. Theoret. Biol. 59, 231-235 (1976).